Microscope system

ABSTRACT

A microscope system includes a casing in which an optical element is housed, an airtight specimen chamber, and an environment control unit that controls temperature and humidity in the specimen chamber and also controls temperature inside the casing. An upper plate of the specimen chamber is an open/close lid opened and closed when inserting or removing a biological specimen. The casing becomes sealed by a bottom plate of the specimen chamber as the specimen chamber is set on the casing.

This is a Division of application Ser. No. 11/286,293 filed Nov. 25,2005, which in turn is a Continuation of Application No.PCT/JP2004/007604 filed Jun. 2, 2004. The disclosure of the priorapplications is hereby incorporated by reference herein in its entirety.

INCORPORATION BY REFERENCE

The disclosure of the following priority applications are hereinincorporated by reference:

-   Japanese Patent Application No. 2003-156810, filed Jun. 2, 2003-   Japanese Patent Application No. 2003-171820, filed Jun. 17, 2003

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a microscope system.

2. Description of Related Art

As rapid progress is made in the field of biotechnology, it has becomeincreasingly important in recent years to be able to observe abiological specimen over an extended period of time or to record animage of the biological specimen while keeping it in an intactcondition. A container in which a biological specimen is placed isfilled with a liquid referred to as a “culture medium” containingnutrients necessary to sustain life. The temperature at the container ismaintained at approximately 37° C., while the humidity inside thecontainer is maintained at a level close to 100%.

Japanese Laid Open Patent Publication No. H5-26802 discloses athermostatic humidified chamber used to sustain both the temperature andthe humidity in a specimen chamber at constant levels and allowmicroscopic observation of the specimen placed inside the specimenchamber through an observation window. In order to prevent condensationat the observation window, the thermostatic humidifier tank includes aheating element.

In such a microscope system, however, a difference in temperaturesbetween the thermostatic humidified chamber and the microscope causesthermal deformation of parts constituting the microscope, which causes aproblem of a focal plane being shifted with time.

SUMMARY OF THE INVENTION

A microscope system according to a first aspect of the present inventionincludes a stand on which a specimen container is placed, anilluminating device that illuminates a specimen inside the specimencontainer, an observation optical system through which a specimen isobserved from below the specimen container, and a drive device thatmoves at least part of the observation optical system along a directionsubstantially perpendicular to an optical axis of the observationoptical system relative to a microscope main unit so as to adjust anobservation position at the specimen. The stand and the illuminatingdevice are fixed onto the microscope main unit. The microscope mayfurther include a casing in which the observation optical system ishoused, an airtight specimen chamber that houses the stand and includesan open/close lid opened and closed when inserting or removing thespecimen container, and an environment control unit that controlstemperature and humidity in the specimen chamber and also controlstemperature inside the casing.

A microscope system according to a second aspect of the presentinvention includes an observation optical system through which aspecimen inside a specimen container is observed, a casing in which theobservation optical system is housed, an airtight specimen chamber thathouses a stand on which the specimen container is placed and includes anopen/close lid opened and closed when inserting or removing the specimencontainer, and an environment control unit that controls temperature andhumidity in the specimen chamber and also controls temperature insidethe casing. It is preferable that the casing becomes sealed as thespecimen chamber is coupled with the casing at a surface other than theopen/close lid. It is preferable that the casing includes a surface atwhich a transparent member is disposed over an observation optical path,that the specimen chamber comprises a surface at which a transparentmember is disposed over the observation optical path, and that thesurface of the casing at which the transparent member is disposed andthe surface of the specimen chamber at which the transparent member isdisposed are optically coupled. Over part or all of the surface of thespecimen chamber, which is coupled with the casing to seal the casing, atransparent portion through which the specimen is microscopicallyobserved may be formed.

It is preferable that an illuminating device be mounted at theopen/close lid. A level of airtightness at the casing may be lower thanthe level of airtightness at the specimen chamber. A drive device may behoused inside the casing.

It is preferable that the observation optical system is an infinityoptical system constituted with a first objective lens and a secondobjective lens, that the first objective lens is housed inside thecasing and is caused to move by the drive device, that the secondobjective lens is disposed outside the casing, and that the secondobjective lens has an aperture large enough to cover a distance overwhich the first objective lens travels along a direction substantiallyperpendicular to the optical axis.

The microscope system according to the first aspect may further includean airtight specimen chamber in which the specimen container is placed,and an environment control unit that controls temperature and humidityin the specimen chamber.

The observation optical system may include an infinity objective lensand an image forming optical system that forms an observation image witha parallel light flux from the objective lens, and the drive device maycontrol a range over which the part of the observation optical systemmoves so as a central ray in a parallel light flux from the specimenpresent within an effective visual field of the objective lens to passthrough an entrance pupil of the image forming optical system.

It is preferable to further include a control device that controls thedrive device so as to set the observation optical system at apredetermined reference position. A control device that controls thedrive device may further be provided, a plurality of mount portions maybe formed at the stand so as to allow a plurality of specimen containersto be placed on the stand, and the control device may control the drivedevice so as to set the observation optical system at one of a pluralityof reference positions set in advance, each in correspondence to one ofthe plurality of mount portions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically shows the overall structure adopted in a microscopesystem achieved in a first embodiment of the present invention;

FIG. 2 schematically shows the overall structure that includes anenvironment control device connected to the microscope system achievedin the first embodiment;

FIG. 3 schematically shows the overall structure of the microscopesystem achieved in a second embodiment of the present invention;

FIG. 4 presents a partial view illustrating the opening/closingstructure adopted for a specimen chamber at the microscope system;

FIG. 5 schematically shows the overall structure of an opticalmicroscope system achieved as a variation of the first embodiment;

FIG. 6 schematically shows the overall structure of the microscopesystem achieved in a third embodiment of the present invention;

FIG. 7 is a diagram provided to facilitate an explanation of the signaloutput from a detector;

FIG. 8 schematically shows the overall structure of the microscopesystem achieved in a fourth embodiment of the present invention;

FIG. 9 shows the structure of a microscope system achieved as avariation of the fourth embodiment;

FIG. 10 schematically shows the overall structure of the microscopesystem achieved in a fifth embodiment of the present invention;

FIG. 11 is a perspective showing the positions of mirrors;

FIG. 12 schematically shows the overall structure of the microscopesystem achieved in a sixth embodiment of the present invention;

FIG. 13 shows variation 1 of the sixth embodiment; and

FIGS. 14A and 14B are plan views, respectively showing the microscopesystem achieved as variation 2 of the sixth embodiment and a culturecontainer.

DESCRIPTION OF PREFERRED EMBODIMENTS First Embodiment

The following is an explanation of a microscope system achieved in thefirst embodiment of the present invention, given in reference todrawings.

FIG. 1 schematically shows the overall structure adopted in an opticalmicroscope system in the first embodiment of the present invention. Inorder to facilitate the explanation, different directions are indicatedalong the axes of the XYZ orthogonal coordinate system, as shown in thefigure.

In the optical microscope system achieved in the first embodiment, aspecimen chamber 10 is stacked on top of a casing 20.

The specimen chamber 10 is an airtight container that includes a bottomplate 11 at which a transparent substrate 1 is disposed and an upperplate 12 on which a transmission-type illuminating device 13 isdisposed. A culture container 14 that holds a biological specimen S isplaced on the transparent substrate 1. The transparent substrate 1,which may be constituted with an optical glass fitted in the bottomplate 11, is utilized as an observation window through which thebiological specimen S is observed.

Now, a structural feature of the upper plate 12 that allows it to beopened and closed as shown in FIG. 4 when the biological specimen S isto be replaced or the like is explained.

In FIG. 4, showing the structure of the specimen chamber, the specimenchamber is opened to the outside. The upper plate 12 is an open/closeplate that is opened/closed as a handle 12 b is operated. It is openedon its left side in the figure via a link mechanism 12 a. Through thisopen side, the biological specimen S can be taken out of or placed intothe specimen chamber, or maintenance work can be performed inside thespecimen chamber 10. This opening/closing structure makes it possible toopen the specimen chamber 10 to the outside independently of the casing20 and thus, the biological specimen S can easily be replaced at anytime. In addition, since the specimen chamber is opened over a widespace, the specimen can be replaced without having to tilt the culturecontainer 14 and without allowing the culture container 14 to come incontact with the wall of the specimen chamber 10.

Between the upper plate 12 and a wall portion of the bottom plate 11, aseal member (not shown) is disposed so as to create a completelyairtight space inside the specimen chamber 10 while the upper plate 12is in a closed state.

The casing 20 is a container in which an optical system 21, a twodimensionally movable stage 31, a vertically movable stage 32 and animage-capturing device 33 of the microscope are housed. The casing 20has an open top. As the specimen chamber 10 is set on the casing 20, thebottom plate 11 closes off the top of the casing 20 and thus, the casing20 becomes airtight. The bottom plate 11 functions as a barrier thatcompletely isolates the inner space of the specimen chamber 10 from theinner space of the casing 20 and thus, the casing 20 keeps itself in anairtight state independently of the specimen chamber 10.

The optical system 21 includes an objective lens 22, an excitation lightilluminating device 23, a light attenuation filter 24, a fluorescencefilter 25, a reflecting mirror 26 and a second objective lens 27.

The two-dimensionally movable stage 31, on which the optical system 21,the vertically movable stage 32 and the image-capturing device 33 areplaced, moves along the x direction and the y direction over ahorizontal plane (over an XY plane). The vertically movable stage 32holds the objective lens 22 and moves along the optical axis of theobjective lens, i.e., along the z direction.

The image-capturing device 33 is disposed near the second objective lens27.

A control unit 41 is connected to the optical system 21, thetwo-dimensionally movable stage 31, the vertically movable stage 32 andthe image-capturing device 33. The control unit 41 is also connected toa personal computer (PC) 42.

When a biological specimen is to be observed over an extended period oftime, the conditions of the specimen environment need to remainconstant. Accordingly, the specimen chamber 10 in which the culturecontainer 14 is placed adopts a sealed structure and an environmentcontrol device 50 detailed below sustains the conditions (thetemperature, the humidity and the CO₂ concentration) of the environmentin which the biological specimen S is placed at constant levels. Inaddition to the conditions of the environment surrounding the biologicalspecimen S, the temperature inside the casing 20 is sustained at aconstant level.

The following is an explanation of the method adopted to adjust theenvironment within the specimen chamber 10 and the method adopted toadjust the temperature inside the casing 20.

FIG. 2 shows the overall structure that includes the environment controldevice 50 connected to the optical microscope system in the firstembodiment shown in FIG. 1. Components already shown in FIG. 1 are notassigned with reference numerals in FIG. 2 and their explanation isomitted. In addition, the control unit 41 and the PC 42 are not includedin FIG. 2 to simplify the illustration.

The environment control device 50 generates a gas achieving a desiredtemperature, a desired humidity level and a desired composition, andcirculates this gas through the specimen chamber 10 and the casing 20.The environment control device 50 includes a humidifier 51, a heater 52,a circulating pump 53 and a gas mixer 54.

Inside the environment control device 50, the humidifier 51 is connectedto the circulating pump 53 via the gas mixer 54. The heater 52 isdirectly connected to the circulating pump 53. In addition, thetemperature inside the humidifier 51 is adjusted by the heater 52 to alevel equal to the temperature inside the heater 52. The gas mixer 54 isconnected through piping with a gas supply unit (e.g., a pressurizedcanister) (not shown). The gas mixer 54, connected to, for instance, agas cylinder filled with CO₂ gas, adjusts the CO₂ concentration insidethe specimen chamber 10.

External connections are achieved for the environment control device 50,through the humidifier 51 connected via a tube 55 to a joint portion 55a at the specimen chamber 10 and through the heater 52 connected via atube 56 to a joint portion 56 a at the casing 20.

The circulating pump 53 includes two pumps P1 and P2 that areindependent of each other. The pump P1 is connected to the piping (tube)55, whereas the pump P2 is connected to the piping (tube) 56. Namely,the piping 55 and the piping 56 constitute circulation systems that areindependent of each other.

The pump P1 at the circulating pump 53 is connected via the tube 55 witha joint portion 55 b disposed at the specimen chamber 10. The pump P2 atthe circulating pump 53 is connected via the tube 56 with a jointportion 56 b at the casing 20. The tubes and the joint portions are allthermally insulated.

The circulation system for the specimen chamber 10, i.e., thecirculation system that includes the piping 55, is indicated with threearrows A. The air adjusted at the gas mixer 54 to achieve a specific gascomposition enters the humidifier 51 where its temperature is adjustedto 37° C. and its humidity is adjusted to 100% RH. The circulating pump53 then feeds the air into the specimen chamber 10 via the tube 55 andthe joint portion 55 a. The air having circulated through the specimenchamber 10 is discharged through the joint portion 55 b and returns tothe circulating pump 53 via the tube 55. Subsequently, the air adjustedto achieve the specific gas composition with the temperature and thehumidity thereof achieving the specific levels is supplied into thespecimen chamber 10 again. Thus, the conditions of the environmentinside the specimen chamber 10 are sustained in specific states.

It is desirable to install a temperature sensor (not shown) formonitoring the temperature inside the specimen chamber 10 at a locationas close as possible to the culture container 14, provided that itspresence does not pose any hindrance to observation.

The circulation system for the casing 20, i.e., the circulation systemthat includes the piping 56, is indicated with three arrows B. The airheated to 37° C. with the heater 52 is fed by the circulating pump 53into the casing 20 via the tube 56 and the joint portion 56 a. The airhaving circulated through the casing 20 is discharged via the jointportion 56 b and returns to the circulating pump 53 via the tube 56.Then, with its temperature adjusted to the specific level, the air issupplied into the casing 20 again. Thus, the temperature inside thecasing 20 is sustained at the predetermined level.

Since the paths of the circulation system for the specimen chamber 10and the circulation system for the casing 20 are independent of eachother, the air in the specimen chamber 10 and the air in the casing 20do not become mixed with each other.

Next, the microscopic observation conducted on the microscope system isexplained.

When observing a transmitted image, the biological specimen S isilluminated with the transmission-type illuminating device 13 and thelight transmitted through the biological specimen S travels through thetransparent substrate 1 before entering the objective lens 22. The lighthaving entered the objective lens 22 is reflected at the reflectingmirror 26, travels through the second objective lens 27 and forms animage on an image-capturing element 33 a (see FIG. 1) of theimage-capturing device 33.

When observing a fluorescent image, light emitted from the excitationlight illuminating device 23 travels through the light attenuationfilter 24 and the fluorescence filter 25 before entering the objectivelens 22 through its bottom. The light having entered the objective lens22 travels through the transparent substrate 1 and is radiated onto thebiological specimen S. This excitation light causes the biologicalspecimen S to emit fluorescent light. The fluorescent light travelsthrough the transparent substrate 1, the objective lens 22 and thefluorescence filter 25, is reflected at the reflecting mirror 26,travels through the second objective lens 27 and forms an image on theimage-capturing element 33 a at the image-capturing device 33.

It is to be noted that a shutter 28 may be disposed on the illuminatinglight emission side of the excitation light illuminating device 23 andthe shutter 28 may be opened only for the fluorescence imageobservation.

The control unit 41 obtains various types of data related to observationconditions, stage movement conditions, photographing conditions and thelike from the PC 42 and outputs control signals generated based upon thedata to the optical system 21, the two-dimensionally movable stage 31,the vertically movable stage 32 and the image-capturing device 33. Inaddition, the control unit 41 outputs various types of control data andimage data to the PC 42.

In response to a control signal provided by the control unit 41, theoptical system 21 adjusts the brightness at the illuminating lightsource, switches the individual filters, switches the observationmagnification factor and adjusts the visual field aperture.

In response to a control signal provided by the control unit 41, thetwo-dimensionally movable stage 31, which includes a drive system (notshown), moves the optical system 21, the vertically movable stage 32 andthe image-capturing device 33 along the x direction and the y direction.This enables observation of different portions of the biologicalspecimen S and, at the same time, makes it possible to verify theposition of the two-dimensionally movable stage 31, i.e., the distancebetween the portion of the biological specimen S being observed and theorigin point position.

Likewise, in response to a control signal provided by the control unit41, the vertically movable stage 32 moves the objective lens 22 alongthe z direction. This enables a focal point adjustment for thebiological specimen S when the observation magnification factor isswitched or when the biological specimen S is replaced.

Through the operations described above, any portion of the biologicalspecimen S can be observed with clarity.

In response to a control signal provided by the control unit 41, theimage-capturing device 33 sets the gain for the CCD, the shutter speedand the timing of the photographing operation executed by interlockingwith the illuminating device. Microscopic image data of the biologicalspecimen S are provided to the PC 42 via the control unit 41 and aredisplayed on a display monitor of the PC 42 as a microscopic image. ThePC 42 is also capable of executing image processing on the microscopicimage and displaying the processed image. In addition, the PC 42 iscapable of displaying the control data indicating the observationconditions, the stage movement conditions, the photographing conditionsand the like described earlier on the display monitor as necessary.

In the first embodiment, the optical system 21, the two-dimensionallymovable stage 31, the vertically movable stage 32 and theimage-capturing device 33 are housed inside the casing 20. Among thesecomponents, the optical system 21 is ranked as the highest prioritycomponent to be housed inside the casing 20, followed by the verticallymovable stage 32, the two-dimensionally movable stage 31 and finally theimage-capturing device 33 in the priority order. In other words, thecomponent disposed at a position closest to the specimen chamber 10 hasthe greatest need to be housed inside the casing 20. Accordingly, theimage-capturing device 33, which has the least need to be housed insidethe casing 20 may be installed outside the casing 20 to reduce thevolumetric capacity of the casing 22 for miniaturization.

In addition, some of the optical members constituting the optical system21 may be disposed outside the casing 20 as well.

FIG. 5 shows a variation of the first embodiment, with the samereference numerals assigned to components identical to those in FIG. 1.The observation optical system that ranges from the objective lens 22through the second objective lens 27 is an infinity optical element. Aparallel light flux formed at the infinite-type optical system istransmitted through a window member 34 disposed at the casing 20 andenters the second objective lens 27 mounted outside the casing 20. Thesecond objective lens 27 and the image-capturing device 35 are bothhoused inside a casing 35 which is attached to the casing 20.

Since the infinity optical system generates a parallel light flux, theimage forming capability is sustained even when the optical system 21placed on the two-dimensionally movable stage 31 moves along the xdirection. In addition, the aperture of the second objective lens 27should be set large enough to tolerate the distance over which theoptical system 21 moves along the y direction. Since the optical system21 moves over a small distance of approximately several mm, the apertureof the second objective lens 27 only needs to be increased byapproximately several mm. Since the moving portion that moves along thex direction and the y direction does not include the second objectivelens 27 and the image-capturing device 33 in this structure, the load isreduced and better response is achieved during movement.

The following is an explanation of the functions of the opticalmicroscope system achieved in the embodiment.

First, the environment inside the specimen chamber 10 and the casing 20is explained. As shown in FIG. 1, the specimen chamber 10 is stacked ontop of the casing 20 and airtight spaces that are independent of eachother are created inside the specimen chamber 10 and the casing 20.

The biological specimen S is placed in the culture medium inside thetransparent culture container 14. The biological specimen S may becells, cell organelles or the like of an animal or plant. In order tokeep the biological specimen S alive for observation over an extendedperiod of time by preventing evaporation of the culture medium, theenvironment inside the specimen chamber 10 needs to be controlled tosustain a predetermined temperature, a predetermined gas composition anda predetermined high humidity level. For instance, the environmentinside the specimen chamber IO may be controlled at 37° C., 100% RH andsustain a CO₂ concentration of 5%. Thus, an environment identical tothat inside the specimen chamber 10 is achieved inside the culturecontainer 14. In addition, in order to prevent leakage of moist gas ormatter evaporated from the culture medium to the outside, the specimenchamber 10 needs to have an airtight structure. A high level ofairtightness is sustained over a long period of time by completelysealing the specimen chamber IO except for at the gas flow intake/outlet(the joint portions 55 a and 55 b).

The temperature inside the casing 20 is maintained at a levelsubstantially equal to the temperature inside the specimen chamber 10,i.e., 37° C. It is not particularly necessary to control the gascomposition and the humidity inside the casing 20. By keeping thetemperatures inside the casing 20 and the specimen chamber 10 equal toeach other, it is assured that no condensation or fogging occurs at thetransparent substrate 1. In addition, since there is no difference inthe temperature between the casing 20 and the specimen chamber 10 toaffect the optical system 21, a focal point change attributable tothermal expansion of the optical components does not occur. Furthermore,since the optical system 21 is not exposed to the high humidityenvironment in the specimen chamber 1 0 while the biological specimen Sis being observed or while the upper plate 12 is opened to replace thebiological specimen S, the optical components and the illuminatingdevice are not damaged.

The level of airtightness achieved at the casing 20 may be lower thanthe level of airtightness that needs to be achieved at the specimenchamber 10, as long as the temperature inside the casing 20 is sustainedat a level substantially equal to the temperature in the specimenchamber 10 and the casing 20 is sealed to such an extent that it ishardly affected by the external environment. Since the casing 20 doesnot need to have an extremely high level of airtightness, electricwiring can be installed and the gas flow intake/outlet can be mountedwith ease.

Second Embodiment

FIG. 3 schematically shows the overall structure adopted in the opticalmicroscope system achieved in the second embodiment of the presentinvention. The same reference numerals are assigned to componentsidentical to those in FIG. 1 and their explanation is omitted.

The optical microscope system in the second embodiment differs from theoptical microscope system in the first embodiment in the connecting area(contact area) where the specimen chamber 10 is stacked on the casing.

The casing 20 in the first embodiment does not include a ceiling plate.As the specimen chamber 10 is stacked atop the casing 20, as shown inFIG. 1, the bottom plate 11 of the specimen chamber 10 becomes a barrierthat separates the inner space of the specimen chamber 10 from the innerspace of the casing 20 so as to keep the specimen chamber 10 and thecasing 20 in an airtight state independently of each other.

A casing 30 in the second embodiment shown in FIG. 3, on the other hand,includes a ceiling plate 3 at which a transparent substrate 2 isdisposed. The ceiling plate 3 also functions as a barrier. Thus,regardless of whether or not the specimen chamber 10 is stacked, thespecimen chamber 10 and the casing 30 are each kept in an airtight stateindependently of each other in the first place. Accordingly, theatmosphere inside the casing 30 remains constant at all times, even whenthe entire specimen chamber 10 is being replaced. The specimen chamber10 adopting the opening/closing structure shown in FIG. 4 can be openedto the outside independently of the casing 30 to allow the biologicalspecimen S to be exchanged at any time with ease. In addition, since thespecimen chamber is opened over a wide space, the specimen can bereplaced without having to tilt the culture container 14 and withoutallowing the culture container 14 to come in contact with the wall ofthe specimen chamber 10.

The lower surface of the bottom plate 11 and the upper surface of theceiling plate 3 may be set in contact with each other or they may be setto range parallel to each other over a very small distance between them.Likewise, the transparent substrates 1 and 2 may be set in contact witheach other or set so as to range parallel to each other over a smalldistance separating them. It is most desirable to set the bottom plate11 and the ceiling plate 3 in contact and the transparent substrates 1and 2 in contact so as to reliably maintain the temperatures inside thespecimen chamber 10 and the casing 30 equal to each other.

If the bottom plate 11 and the ceiling plate 3 are distanced from eachother, atmospheric air at room temperature may flow into the gap betweenthem to cause condensation or fogging at the inner surface of thetransparent substrate 1 or induce focal point fluctuations, an opticalaxis offset and the like at the optical system 21. Such eventualitiesmay be prevented by disposing a sealing member such as an O-ring at theexternal circumferences of the bottom plate 11 and the ceiling plate 3.

While the problems described above may be averted, there is still anoptical problem to be addressed if the transparent substrates 1 and 2are set apart from each other. Namely, since there will be air presentbetween the transparent substrates 1 and 2, reflection occurs for atotal of two times, at their surfaces facing opposite each other, whichleads to a light quantity loss. Such a loss may be prevented byoptically integrating the transparent substrates 1 and 2. For instance,the gap between the transparent substrates 1 and 2 may be filled withliquid immersion oil with a refractive index equal to that of thetransparent substrates 1 and 2.

It is to be noted that the transparent substrate 1 disposed at thebottom plate 11 and the transparent substrate 2 disposed at the ceilingplate 3 each only need to have an area large enough to cover, at least,the observation optical path. In addition, the entire bottom plate 11may be constituted with the transparent substrate 1, and the entireceiling plate 3 may be constituted with the transparent substrate 2.

Operational effects similar to those in the first embodiment areachieved in a structure that includes the environment control device 50described earlier in conjunction with the optical microscope system inthe second embodiment shown in FIG. 3.

In addition, the casing in the optical microscope system in the secondembodiment, too, can be provided as a compact unit by adopting astructure such as that shown in FIG. 5, to achieve operational effectsidentical to those in the first embodiment.

The basic operational effects of the optical microscope system in thefirst embodiment and the optical microscope system in the secondembodiment are similar to each other. Namely, the space inside thespecimen chamber 10 and the space inside the casing 20 or 30 are eachkept in an airtight state independently of each other, and thus, thecasing 20 or 30 is not exposed to the high humidity environment insidethe specimen chamber 10. As a result, the optical components and theilluminating device are protected from damage. Since the specimenchamber 10 can be opened to the outside independently of the casing 20or 30, the specimen can be replaced at any time with ease.

In addition, since the specimen chamber 10 and the casing 20 or 30 aredisposed adjacent to each other and their internal temperatures aremaintained at levels equal to each other, the transparent substrate 1remains free of condensation or fogging, and any instability or changeoccurring over time at the optical system 20 is kept to a minimum. As aresult, microscopic observation and recording can be conducted in astable manner over a long period of time.

Furthermore, with the optical system housed in the casing 20 or 30, themicroscope is set in a state similar to that achieved by installing themicroscope in a darkroom. As a result, a fluorescence image observationcan be conducted without having to darken the room.

The following is an explanation of variations of the present invention.

The optical microscope systems in the first and second embodiments bothinclude the two-dimensionally movable stage 31, which is used to movethe optical system 21 for observation of different portions of thebiological specimen S. In other words, the specimen chamber 10 and thetransmission-type illuminating device 13 are fixed relative to thecasing 20 constituting the microscope main unit. Instead, a structurethat includes a fixed optical system 21 and allows movement of theculture container 14 containing the biological specimen S may beadopted. Since only the culture container 14 needs to be moved in thisstructure, the moving mechanism can be miniaturized and the entireoptical microscope system can be provided as a more compact unit.

In the optical microscope system achieved in either the first embodimentor the second embodiment, the specimen chamber 10 is stacked on thecasing 20 or 30. Instead, the casing 20 or 30 may be stacked on top ofthe specimen chamber 10. This structure should be adopted in an uprightmicroscope instead of an inverted microscope. Since the specimen doesnot need to be observed through the culture container 14, even abiological specimen present outside the culture medium can be observedwith a microscope adopting this structure. However, if the casing 20 hasan open bottom, the optical system of the upright microscope must bemounted at a side plate or the upper plate of the casing 20.

As described above, in the first and second embodiments of the presentinvention, airtight spaces independent of each other are formed in thespecimen chamber 10 and the casing 20 or 30 to facilitate temperatureand humidity control. Thus, an optical microscope system ideal forobservation of a biological specimen over an extended period of time,which does not allow the focal plane to become unstable, can beprovided.

Third Embodiment

Next, the microscope system achieved in the third embodiment isexplained. FIG. 6 shows the structure of the microscope system achievedin the third embodiment. The same reference numerals are assigned tocomponents having functions similar to those in the first embodimentshown in FIGS. 1 and 2. The explanation focuses on the featuresdifferentiating the third embodiment from the first embodiment.

As in the first embodiment, the microscope system achieved in the thirdembodiment includes the specimen chamber 10 in which the culturecontainer 14 holding a biological specimen S is placed and the casing 20in which an optical system, an image-capturing device 117 and the likeof the microscope are housed. In addition, the environment controldevice 50 controls the environment inside the specimen chamber 10 at,for instance, 37° C., 100% RH with a CO₂ concentration of 5%, andsustains the temperature inside the casing 20 at a constant level (e.g.,37° C.).

As shown in FIG. 6, a base (microscope main unit) 111 of the microscopesystem, a movable stage 119 fixed onto the base 111, a microscope casing115 fixed onto the movable stage 119, an objective lens 116, theimage-capturing device 117 used to photograph an observation image andthe like are housed inside the casing 20. The objective lens 116 and theimage-capturing device 117 are disposed at the microscope casing 115.The objective lens 116 is disposed under the culture container 14, at aposition corresponding to the position of the transmission-typeilluminating device 13. Thus, the biological specimen S inside theculture container 14 is illuminated from above in FIG. 6 with thetransmission-type illuminating device 13 and the light having beentransmitted through the biological specimen S and having passed throughthe transparent substrate 1 is observed through the objective lens 116.It is to be noted that the objective lens 116 and a reflecting mirror118 constitute an observation optical system of the microscope system inFIG. 6.

The light from the objective lens 116 is reflected at the reflectingmirror 118 and forms an image on an image-capturing surface of theimage-capturing device 117. While the image-capturing device 117 may beconstituted with a confocal microscope device, a CCD camera or the like,an explanation is given in reference to the third embodiment on anexample in which the image-capturing device is constituted with a CCDcamera. A controller 100 is a control device that executes overallcontrol of the microscope and includes an image processing unit forprocessing image-capturing signals from the image-capturing device 117and the like. The image-capturing signals provided by theimage-capturing device 117 are processed at the image processing unitinside the controller 100 and the resulting specimen image (digitalimage) having been captured at the image-capturing device is displayedat a monitor 101. The monitor 101 may be constituted with a liquidcrystal display element (LCD) or the like. A stage control device 103controls the movement of the movable stage 119. Stage movementinstructions for moving the stage so as to observe a desired portion ofthe biological specimen S and instructions for various types ofmicroscope adjustments including optical filter switching, apertureswitching, objective lens switching and illuminating light quantityadjustment are issued via an operation unit included in a command unit102.

The microscope casing 115 fixed onto the upper surface of the movablestage 119 can be moved via the movable stage 119 along the x direction,the y direction and the z direction in the figure relative to the base111. It is to be noted that the movable stage 119 may only move alongthe x direction and the y direction with the objective lens 116 allowedto move along the z direction instead. The movable stage 119 is drivenby a pulse motor, a DC motor equipped with an encoder or the like, andthe distance over which the movable stage travels can be measured bycounting the number of output pulses.

An origin point position (reference position) is set in advance for themovable stage 119. For instance, the origin point may be set at theposition at which the observation position is adjusted to the center ofthe culture container 14. At the movable stage 119, a detector 41 isdisposed in correspondence to the origin point position. The detector41, which may be constituted with a photo interrupter or the like,generates an origin point signal each time a shielding plate used as areference 40 travels past the detector 41. As the movable stage 119 isset at the position set in correspondence to the origin point signalprovided by the detector 41, the optical axis of the objective lens 116is set aligned at the center of the culture container 14. The followingexplanation is given by assuming that the detector is constituted with aphoto interrupter. It is to be noted that the detector 41 and thereference 40 are installed as a unit along both the x direction and they direction.

The movable stage 119 which causes the microscope casing 115 to movealong the x direction and the y direction is allowed to assume two modesof movement, i.e., a coarse movement and a fine movement to a positiononly slightly distanced from the measurement point. The fine movementoccurs within the specimen over a distance of approximately several mmat the most. The fine movement is controlled by using pulses.

The coarse movement is explained first. As the reference 40 moves pastthe detector 41, a signal I such as that shown in FIG. 7 is output fromthe detector 41. Such an output signal I can be identified in advancewith accuracy. When positioning the movable stage 119, the position ofthe movable stage 119 along the x direction is adjusted through feedbackcontrol so as to keep the signal I within the range of I1 to I1+ΔI.Thus, the position of the movable stage 119 is set within the range ofx1 to x1+Δx. By narrowing the range of ΔI as much as possible, themovable stage can be positioned with accuracy in the order of 0.1 μm.

The distance over which the movable stage is moved in the fine movementis controlled by counting pulses. If, for instance, the minimumtraveling distance of the movable stage 119 is 5 μm per pulse, itsmovement over 10 pulses will change the observation position by 50 μm.

Fourth Embodiment

The microscope system achieved in the fourth embodiment is nextexplained. FIG. 8 schematically shows the structure adopted in themicroscope system achieved in the fourth embodiment. The same referencenumerals are assigned in FIG. 8 to components having functions identicalto those in the third embodiment shown in FIG. 6. The followingexplanation focuses on the features that distinguish the fourthembodiment from the third embodiment. It is to be noted that themicroscope system in the fourth embodiment does not include the specimenchamber 10, the casing 20 and the environment control device 50.

FIG. 8 illustrates observation of a specimen (biological specimen) in aculture container 113, illuminated with transmission light. A stand 112and the movable stage 119 are fixed onto the base 111 of the microscopesystem. An observation opening 112 b is formed at a specimen mountportion 112 a of the stand 112, and the culture container 113 containingthe specimen is placed over the area where the opening 112 b is formed.A support 112 c used to support a manipulator is disposed at thespecimen mount portion 112 a. In the example presented in the figure, adosing tube 112 d is attached to the support 112 c.

The microscope casing 115 is fixed onto the movable stage 119. Theobjective lens 116 and the image-capturing device 117 used to photographan observation image are disposed at the microscope casing 115. Atransmission-type illuminating device 114 is disposed at the stand 112above the specimen mount portion 112 a. The objective lens 116 disposedat the microscope casing 115 is positioned under the specimen mountportion 112 a at which the culture container 113 is placed, so as toface opposite the transmission-type illuminating device 114. Namely, thespecimen contained in the culture container 113 is illuminated by thetransmission-type illuminating device 114 from above in the figure andthe light having been transmitted through the specimen and passedthrough the opening 112 b is observed through the objective lens 116.

As in the third embodiment, the detectors 41 are disposed at the movablestage 119 and the references 40 are disposed at the microscope casing115. The movable stage 119 makes coarse movement based upon signalsoutput from the detectors 41 and makes fine movement in correspondenceto pulses so as to adjust the position of the microscope casing 115.Since the movable stage makes the coarse movement and the fine movementby adopting a method similar to that explained in reference to the thirdembodiment, a repeated explanation thereof is not provided.

In the microscope system shown in FIG. 8, the stand 112 at which theculture container 113 is placed is a fixed stand and the microscopecasing 115 is allowed to move along three directions, i.e., the xdirection, the y direction and the z direction, relative to the stand112.

If the observation position of the specimen is adjusted by moving astage supporting the culture container 113 in an inverted microscope inwhich the solution inside the culture container 113 is rotated via thedosing tube 112 d or the membrane voltage at a cell is measured, thetube for the solution rotation may become disengaged or the patch usedin the potential measurement may become disengaged. If the entiremicroscope is made to move instead of the specimen stage in an uprightmicroscope system, the front end of the objective lens may come incontact with the solution in the culture container 113 and thus, therange of movement will become limited. In addition, the high-speedmovement of the entire microscope, which is considerable in size, willinduce a vibration that may cause disengagement of the tube used torotate the solution or the patch used in the potential measurement.

However, the microscope system achieved in the fourth embodiment, whichadopts the structure described above, allows the observation point to beadjusted without having to move the culture container 113 or the dosingtube 112 d so as to keep the specimen inside the culture container 113in a stable condition. In addition, it does not require the illuminatingdevice 114 to move and thus has a smaller moving portion that is able tomove at high-speed without causing significant vibration.

FIG. 9 shows a variation of the fourth embodiment.

The movable stage 119 and the stand 112 are fixed onto the base 111.Three specimen mount portions 112 a, each fitted with an optical glass,are formed at the stand 112. It is to be noted that instead of fittingglass in the specimen mount portions, culture containers 113 may beplaced at the specimen mount portions to be held as a seal. The culturecontainers 113 are set at these specimen mount portions 112 a. Namely,three culture containers 113 set on the stand 112 can be observed insequence with the microscope system shown in FIG. 9. A cover C withthree illuminating devices 114 each disposed in correspondence to one ofthe specimen mount portions 112 a is mounted on the stand 112 so as tocover the culture containers 113. As a result, the culture containers113 are placed in an airtight environment. The microscope casing 115 andthe movable stage 119, on the other hand, are not set in an air tightenvironment.

It is to be noted that an environment control device similar to thatused in the third embodiment may be utilized to control the environment(the temperature and humidity) inside the cover C (inside a specimenchamber).

Detectors 41A, 41B and 41C each corresponding to one of the specimenmount portions 112 a are disposed along the x direction at the movablestage 119. The detectors 41A through 41C, similar to the detectors 41described earlier, each generate an origin point signal as the positionof the reference 40 becomes aligned with the position of the detector41A, 41B or 41C while the microscope casing 115 is moved along the xdirection via the movable stage 119. Namely, by using the detectors 41Athrough 41C, the objective lens 116 can be set at positions at which theindividual specimen mount portions 112 a are located. It is to be notedthat although not shown, a detector 41 and a reference 40 used commonlyin conjunction with the three specimen mount portions 112 a are disposedalong the y direction.

The movable stage 119 makes coarse movement to move the objective lens116 between different culture containers 113, and the objective lens 116is positioned at a specific specimen mount portion 112 a based upon asignal provided by the detector 41 a, 41B or 41 c. The observation pointwithin a given culture container 113 is adjusted through the finemovement as explained earlier.

Fifth Embodiment

FIG. 10 shows the microscope system achieved in the fifth embodiment ofthe present invention. The microscope system achieved in the fourthembodiment in FIG. 8 is characterized in that the entire observationoptical system is moved and that the optical system is miniaturizedthrough the use of a finite-type objective lens and a finite-typeoptical system. In the fifth embodiment, on the other hand, only part ofthe observation optical system is allowed to move. In addition, in orderto move only the part of the observation optical system that includesthe objective lens, an infinity objective lens is used in conjunctionwith an optical system constituted with an image forming lens and animage-capturing device disposed at a fixed portion.

The same reference numerals are assigned in FIG. 10 to componentsidentical to those in the fourth embodiment shown in FIG. 8. Theexplanation focuses on features of the embodiment that differentiate itfrom the fourth embodiment.

A stand 212, a movable stage 219 and a microscope casing fixed portion220 are fixed to a base 211 of the microscope system. The movable stage219 is controlled by a stage control device 103. An observation opening212 b is formed at a specimen mount portion 212 a of the stand 212, andthe culture container 113 containing the specimen is placed over thearea where the opening 212 b is formed. At a support 212 c used to holda manipulator, which is disposed at the specimen mount portion 212 a, adosing tube 212 d is attached as in the fourth embodiment. Thetransmission-type illuminating device 114 is disposed at the stand 212so that the specimen inside the culture container 113 is observed withtransmission illuminating light.

The microscope casing in the microscope system achieved in the fifthembodiment is constituted with two separate units, the fixed portion 220and a moving portion 215. The microscope casing moving portion 215 isfixed onto the movable stage 219. The microscope casing moving portion215 fixed onto the upper surface of the movable stage 219 is allowed tomove via the movable stage along the x direction, the y direction andthe z direction in the figure. As in the fourth embodiment, thedetectors 41 are disposed along the x axis and the y axis at the movablestage 219. At the microscope casing moving portion 215, the references40 are disposed. The moving mechanism used to move the movable stage 219is similar to that employed in conjunction with the movable stage 119described earlier, achieving a function similar to that explained inreference to the movable stage 119, when moving the observation point.Thus, its explanation is not provided.

At the microscope casing moving portion 215, and objective lens 216 anda reflecting mirror 218 are disposed. At the microscope casing fixedportion 220, an epi-illumination device 214 is disposed, as anadditional illuminating device independent of the transmission-typeilluminating device 114 disposed at the stand 212. In addition, theimage-capturing device 117 that captures an observation image andoptical members 221, 222, 223 and 224 used to guide the illuminatinglight from the epi-illumination device 214 toward the microscope casingmoving portion 215 and form the observation image at the image-capturingdevice 117 are disposed at the microscope casing fixed portion 220. Theoptical members 223 and 224 are lenses, the optical member 222 is areflecting mirror and the optical member 221 is a beam splitter. It isto be noted that the optical member 223 is used as the image formingoptical system in the microscope system.

While the specimen can be observed under transmission illuminating lightor under epi-illumination light in the microscope system achieved in thefifth embodiment, the following explanation focuses on observationconducted under epi-Ilumination light.

Illuminating light emitted from the epi-illumination device 214 travelsthrough the lens 224, the reflecting mirror 222 and the beam splitter221 and then enters the reflecting mirror 218 at the microscope casingmoving portion 215. The illuminating light reflected at the reflectingmirror 218 enters the culture container 113 via the objective lens 216and illuminates a specific area of the specimen. The light having exitedthe specimen is guided to the image-capturing device 117 via theobjective lens 216, the reflecting mirror 218, the beam splitter 221 andthe lens 223 and the observation image is formed on the image-capturingsurface of the image-capturing device 117.

The objective lens 216 is an infinity optical system, and thus, thelight having departed the focal plane of the specimen becomes a parallellight flux 225 after passing through the objective lens 216, and theparallel light flux 225 is guided to the beam splitter 221 by thereflecting mirror 218. In addition, the illuminating light emitted fromthe epi-illumination device 214 becomes a parallel light flux at thelens 224, and the parallel illuminating light flux enters the reflectingmirror 218 via the reflecting mirror 222 and the beam splitter 221.

The microscope system in FIG. 10 adopts a structure that allows at leastthe rays at the center of the parallel light flux formed with the lightfrom the specimen present within the effective visual field of theobjective lens 216 to pass through an entrance pupil of the imageforming optical system even when the microscope casing moving portion215 is made to move via the movable stage 219. Since a stroke of themicroscope casing moving portion 215 is approximately several mm, theapertures of the optical members 221 and 223 are set to larger values byan extent corresponding to the movement of the microscope casing movingportion 215 along the y direction. In other words, since the distanceover which the microscope casing moving portion 215 moves within itsallowable range is approximately several mm, the apertures of theoptical members 221 and 223 only need to be increased in size by severalmm in correspondence. Since only part of the observation optical systemis made to move instead of the entire observation optical system, theload on the microscope casing moving portion 215 is reduced, whichimproves the response.

It is to be noted that the movable stage 219 may need to move with agreater stroke along the x direction and the y direction in order toenable observation of a plurality of culture containers or a largeculture container 113. In such a case, a mirror M1 for reflecting thelight along the y direction should be disposed together with theobjective lens 216 at a y direction moving portion 219 a of the movablestage 219 and a mirror M2 for reflecting the light along the x directionshould be disposed, together with the mirror MI, the objective lens 216and the y direction moving portion 219 a, at an x direction movingportion 219 b of the movable stage 219, so as to prevent the light fluxfrom becoming offset from the beam splitter 221, as shown in FIG. 11.

As described above, in the fifth embodiment, too, the observationposition can be adjusted by moving the microscope casing moving portion215 relative to the culture container 113 placed on the stand 212. Thus,advantages similar to those of the fourth embodiment can be achieved. Inaddition, since the light flux from the specimen becomes the parallellight flux 225, the microscope casing can be split into the fixedportion 220 and the moving portion 215 of which only the moving portion215 is made to move relative to the stand 212. This reduces the weightof the object to be moved via the movable stage 219, which, in turn,allows the object to be moved at greater speed. In addition, the extentof vibration occurring as the movable stage starts/stops moving can bereduced.

Sixth Embodiment

FIG. 12 shows the microscope system achieved in the sixth embodiment ofthe present invention, which allows an observation with transmissionilluminating light. In the sixth embodiment, the environment in thespecimen chamber containing the biological specimen S is controlled andthe temperature in the casing where the microscope is housed issustained at a constant level, as in the third embodiment explainedearlier. It is to be noted that while a single culture container 14 isplaced inside the specimen chamber 10 in the third embodiment, fiveculture containers 14A through 14E are placed in a single row inside thespecimen chamber 10 in the sixth embodiment shown in FIG. 12.

It is to be noted that while the system shown in FIG. 12, too, includesthe controller 100, the monitor 101, the command unit 102 and the stagecontrol device 103 similar to those shown in FIG. 6, they are notincluded in the illustration. In addition, the piping 55 and the piping56 are respectively connected to the joint portion 55 a, at the specimenchamber 10 and the joint portion 56 a at the casing 20, with theenvironment control device 50 (not shown) similar to that shown in FIG.6 connected via the pipings 55 and 56.

Although hidden under the culture containers 14A through 14E in FIG. 12,five observation windows are fitted at the bottom plate 11 as in thespecimen chamber 10 shown in FIG. 6, and the culture containers 14Athrough 14E are set over the observation windows. It is to be noted thatinstead of disposing glass to function as the observation windows,culture containers directly set in the openings may be used as windows.At the open/close lid (upper plate) 12 of the specimen chamber 10, fivetransmission-type illuminating devices 13A through 13E are disposed eachat a position facing opposite one of the observation windows.

Inside the casing 20, a microscope comprising the base 111, the movablestage 119, the microscope casing 115 at which the objective lens 116 isdisposed and the image-capturing device 117 (not shown) is installed. Itis to be noted that a front surface 201 of the casing 20 is taken off inFIG. 12 to better show the internal structure adopted in the casing 20.Near the bottom of the casing 20, a guide 90 and a feed screw 91 bothextending to the left and the right (along the x axis) are disposed. Amotor 92 rotationally drives the feed screw 91. The motor 92 maybe apulse motor or a DC motor equipped with an encoder. The guide 90 isinserted through the base 111 and the feed screw 91 is interfixedthrough the base 111. As the motor 90 drives the feed screw 91 to rotateforward or backward, the base 111 is caused to move to the left or theright along the guide 90. The motor 90 is controlled by the stagecontrol device 103.

The movable stage 119, the objective lens 116, the microscope casing 115and the image-capturing device 117 adopt structures similar to thoseshown in FIG. 6. At the movable stage 119, the detectors 41 used toposition the movable stage 119 at the origin point are disposed, one formovement along the x direction and the other for movement along the ydirection. At the microscope casing 115, the references 14 are disposedeach in correspondence to one of the detectors 41. In addition, at thebottom plate of the casing 20, detectors 93A through 93E used to set thebase 111 at the position of the individual culture containers 14Athrough 14E are disposed. A reference 94 is disposed at the base 111 tobe used in conjunction with the detectors 93A through 93E. As are thedetectors 41, the detectors 93A through 93E are each constituted with aphoto interrupter or the like, and as are the references 40, thereference 94 is constituted with a shielding plate.

In the sixth embodiment, the culture containers 14A through 14E areobserved sequentially by moving a single microscope along the xdirection. FIG. 12 shows the base 111 of the microscope set at theobservation position for observing the culture container 14C, with theobservation point of the objective lens 116 positioned at the center ofthe culture container 14C. The positioning operation is executed byusing the detector 93C and the reference 94.

In this state, the feed screw 91 is driven by the motor 92 to rotateforward to the observation position for the next culture container 14B.Once the detector 93B detects the reference 94, the motor 92 is stoppedand the base 111 is set at the position determined by the detector 93B.As a result, the observation point of the objective lens 116 ispositioned at the center of the culture container 14B. The subsequentadjustment of the observation point inside the culture container 14B ismade as has been explained in reference to the previous embodiment.

Biological specimens are observed over an extended period of timenormally by observing the individual specimens in sequence overpredetermined time intervals (e.g., over 15-minute intervals). They maybe observed in the order of, for instance, the culture container 14A→theculture container 14B→the culture container 14C→the culture container14D→the culture container 14E over the predetermined time intervals.Under such circumstances, the lens can be positioned quickly andaccurately through the coarse movement between the individualcontainers, which is achieved by using the motor 92 and the detectors93B through 93E. In addition, even though the observation is conductedrepeatedly over the predetermined time intervals, the repeatability ofthe observation positions is very high.

Variation 1 of the Sixth Embodiment

An explanation is given above in reference to the sixth embodiment on anexample in which a plurality of culture containers 14A through 14E setin a single row are observed with a single microscope. In variation 1shown in FIG. 13, culture containers 14A through 14C are set so as toform a circular arc. FIG. 13 is a plan view of the microscope systemtaken from above, with the stand at which the culture containers 14Athrough 14C are set not included in the illustration. It is to be notedthat while the specimen chamber 10, the casing 20 and the environmentcontrol device 50 explained earlier are not shown in FIG. 13, themicroscope system may or may not include these, depending upon thespecific purposes of use.

An xy stage 158 to which a microscope casing 152 is fixed is set on topof a rotating stage 159. Thus, the xy stage 158 on which the microscopecasing 152 is stacked can be made to rotate around a rotational axis 151via the rotating stage 159. An objective lens 153 and theimage-capturing device 117 are disposed at the microscope casing 152.Reference numerals 156A, 156B and 156C indicate detectors disposedrespectively in correspondence to the culture containers 14A through14C, and the detectors 156A through 156C are disposed so as to form acircular arc. At the microscope casing 152, a reference 155 is disposed.

It is to be noted that the structures of the reference 155 and thedetectors 156A through 156C are similar to those of the references 40and the detectors 41A through 41C described earlier. In variation 1,too, an origin point signal is generated each time the reference 155moves past the detector 156A, 156B or 156C as the microscope casing 152rotates. In variation 1, the coarse movement is achieved through therotating movement via the rotating stage 159 and the fine movement isachieved via the XY stage 158.

Variation 2 of the Sixth Embodiment

FIG. 14A is a plan view of the microscope system achieved in variation2, with a culture container 171 such as that shown in FIG. 14B placed atthe stand (not shown) of the microscope system. It is to be noted thatFIG. 14A does not include illustration of the stand. While the specimenchamber 10, the casing 20 and the environment control device 50 are notincluded in the illustration of variation 2, the microscope system invariation 2 may or may not include these, depending upon the specificpurposes of use. As shown in FIG. 14B, a plurality of wells 172 each tohold a specimen are formed in a lattice pattern at the culture container171. The specimen is placed in each of the wells 172. An x stage 167 isfixed onto a base 160 of the microscope system, and a movable portion167B moves along the x direction relative to a fixed portion 167A of thex stage 167.

The movable portion 167B also functions as a fixed portion of a y stage,and a y movable portion 167C capable of moving along the y direction isdisposed at the movable portion 167B. A microscope casing 161 is fixedonto the y movable portion 167C which includes a z movement mechanismfor moving the microscope casing 161 along the z direction. An objectivelens 162 and the image-capturing device 117 are disposed at themicroscope casing 161.

A plurality of detectors 168 are disposed side-by-side along the xdirection at the fixed portion 167A of the x stage 167. The number ofdetectors 168 matches the number of wells 172 set along the x directionat the culture container 171 and the detectors 168 are disposed overintervals equal to the intervals over which the wells 172 are formedalong the x direction. An x reference 170 x is disposed at the movableportion 167B to be used in conjunction with the detectors 168.

A plurality of detectors 166 is disposed side-by-side along the ydirection at the movable portion 167B. The number of detectors 166matches the number of wells 172 set along the y direction at the culturecontainer 171 and the detectors 166 are disposed over intervals equal tothe intervals along which the wells 172 are formed along the ydirection. In addition, a y reference 170 y is disposed at the y movableportion 167C, to be used in conjunction with the detectors 166. Sincethe references 170 x and 170 y and the detectors 168 and 166 adoptstructures similar to those of the references 40 and the detectors 41Athrough 41C described earlier, their explanation is omitted.

In variation 2, the movable portion 167B is allowed to make a coarsemovement along the x direction, i.e., it is allowed to move from a givenwell to the next well along the x direction, based upon origin pointsignals provided by the detectors 168. In addition, the movable portion167C is allowed to make a coarse movement along the y direction, i.e.,it is allowed to move from one well to the next well along the ydirection, based upon origin point signals provided by the detectors166. In this example, too, the observation position within a given well172 is adjusted through fine movement of the movable portions 167B and167C effected based upon pulse signals.

An explanation is given above in reference to the third through sixthembodiments on an example in which the positioning operation is executedby utilizing detectors constituted with photo interrupters. However, thepresent invention is not limited to this example and the positioningoperation may instead be executed by using a mechanical positioningdevice such as a click mechanism for positioning. In addition, as longas the features characterizing the present invention remained intact,the present invention is not limited to the examples presented in theembodiments in any way whatsoever.

As explained above, the observation position is adjusted in themicroscope systems achieved in the third through sixth embodiments bymoving the observation optical system through which the culturecontainer is observed from below. This structure remains free ofproblems such as the tube for solution rotation and the patch used inthe potential measurement, which are attached to the specimen(biological specimen), becoming disengaged even when the observationoptical system is made to move at high speed to adjust the observationposition.

While an explanation is given above on an example in which the presentinvention is adopted in the microscope system that employs animage-capturing device to capture an image of a biological specimen, thepresent invention may also be adopted in a microscope system thatincludes an eyepiece lens or the like to allow the user to directlyobserve a biological specimen.

The above described embodiments are examples, and various modificationscan be made without departing from the spirit and scope of theinvention.

1. A microscope system, comprising: an airtight specimen chamber, inwhich a specimen is placed, that maintains an environmental condition inthe specimen chamber; a first casing disposed adjacent to the specimenchamber, that houses an objective lens for observing the specimen; asecond casing disposed adjacent to the first casing, that houses animage forming lens for forming an image of the specimen from theobjective lens onto an image sensor; and an environment control unitthat controls temperature and humidity in the specimen chamber and alsocontrols temperature inside the first casing, wherein environmentalconditions of the specimen chamber, the first casing, and the secondcasing are set independent of each other.
 2. A microscope systemaccording to claim 1, wherein the control unit adjusts a temperature inthe specimen chamber and a temperature in the first casing to a sametemperature.
 3. A microscope system according of claim 1, wherein theobjective lens in the first casing and the image forming lens in thesecond casing form an infinity optical system.
 4. A microscope systemaccording to claim 1, further comprising: a transmission illuminatingdevice that irradiates a transmission illumination light to the specimenin the specimen chamber; and an epi-illumination device that irradiatesan epi-illumination light to the specimen in the specimen chamber.